Functional changes of intestinal intraepithelial lymphocytes during acute graft versus host disease: correlation with phenotype.

Abstract

While the pathological characteristics of acute graft versus host disease (GvHD) have been defined for many target organs, little attention has been paid to the functional changes to lymphocytes in target organs such as the liver and small intestine. We have shown previously, utilizing a nonlethal parent (C57BL/6J) into the F1 (C57BL/6J x DBA2J F1) GvHD model, that the intestinal mucosa is infiltrated exclusively by donor T cells with a CD8+ phenotype during the first 3 weeks post-GvHD induction. The present study investigated the functional changes associated with the phenotypic changes of intestinal intraepithelial lymphocytes (IEL) during the acute phase of GvHD. IEL displayed specific anti-host cytolytic activity during the second and third week after GvHD induction. In addition, enhanced cytolytic activity, detected in the presence of anti-CD3 antibody, was apparent during the second through fourth week, with a peak in the third week after GvHD induction. The IEL also showed enhanced proliferative responses to immobilized anti-CD3 during the first 2 weeks of acute GvHD, while profound inhibition of proliferation was observed in the splenocyte population of the same animals. During weeks 2 and 3 post-GvHd induction, the V beta distribution of host IEL remained unchanged while the V beta distribution of infiltrating donor CD8+ cells resembled that of the donor IEL population. In the small intestine, the increased cytolytic and proliferative activity of IEL during the course of the disease may provide a rationale for the involvement of this organ in the pathology associated with GvHD.